Abstract
This double-blind placebo controlled, parallel design clinical trial compared the therapeutic effects of the addition of lithium or placebo to haloperidol in 21 seriously ill state hospital patients with DSM-III-R schizophrenia, who did not have concurrent affective disorders and who had not responded to previous trials of conventional antipsychotic medication. During a baseline period of 6 weeks, patients were switched to a stable dose of haloperidol (mean ± SD dose=13.6±8.1 mg/day). Patients were then randomized to receive either lithium or placebo in addition to haloperidol for 8 weeks (mean ± SD lithium level =0.98±0.13 mEq/1). Symptoms and side effects were assessed weekly. Improvement in symptoms correlated with the non-blind adjustment of antipsychotic dose, but not with lithium or placebo treatment. Side effects ratings did not differ between the two groups, but one patient developed a reversible delirium associated with combined lithium/haloperidol treatment. For these long-term, severely ill patients, combined treatment afforded no advantage over treatment with haloperidol alone.
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References
Addonizio G (1985) Rapid induction of extrapyramidal side effects with combined use of lithium and neuroleptics. J Clin Psychopharmacol 5:296–298
Addonizio G, Susman VL (1991) The neuroleptic malignant syndrome: a clinical approach. Mosby Year Book, St Louis, MO
Alexander PE, Van Kammen DP, Bunney WE (1979) Antipsychotic effects of lithium in schizophrenia. Am J Psychiatry 136:282–287
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd ed, revised (DSM-III-R) American Psychiatric, Washington, DC
Andreason NC (1982) Negative symptoms in schizophrenia: definition and reliability. Arch Gen Psychiatry 39:784–788
Baastrup PC, Hollnagel P, Sorensen R, Schou (1976) Adverse reactions in treatment with lithium carbonate and haloperidol. JAMA 23:2645–2646
Baldessarini RJ (1985) Antipsychotic agents. In: Baldessarini RJ (ed) Chemotherapy in psychiatry: principles and practice. Harvard University Press, Cambridge, MA, pp 14–92
Barklage NE, Jefferson JW (1987) Alternative uses of lithium in psychiatry. Psychosomatics 28:239–244, 249–253, 256
Barnes TRE (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154:672–676
Biederman J, Lerner Y, Belmaker RH (1979) Combination of lithium carbonate and haloperidol in schizo-affective disorder. Arch Gen Psychiatry 36:327–333
Cade JFJ (1949) Lithium salts in the treatment of psychotic excitement. Med J Aust 2:349–352
Carman JS, Bigelow LB, Wyatt RH (1981) Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients. J Clin Psychiatry 42:124–128
Christison GW, Kirch DG, Wyatt RJ (1991) When symptoms persist: choosing among alternative somatic treatments for schizophrenia. Schizophr Bull 17:217–259
Cohen WJ, Cohen NH (1974) Lithium carbonate, haloperidol and irreversible brain damage. JAMA 230:1283–1287
Cooper TD, Simpson GM (1976) The 24-hour lithium level as a prognosticator of dosage requirements. Am J Psychiatry 133:440–443
Delva NJ, Letemendia FJJ (1982) Lithium treatment in schizophrenia and schizo-affective disorders, Br J Psychiatry 141:387–400
Del Zompo M, Bocchetta A, Burrai C, Melis M, Corsini GU (1984) Lithium treatment in schizoaffective patients. In. Corsini GU (ed) Current trends in lithium and rubidium therapy. MTP Lancaster, England, pp 143–150
Donaldson SR, Gelenberg AJ, Baldessarini RJ (1983) The pharmacologic treatment of schizophrenia: a progress report. Schizophr Bull 9:504–527
Folstein MF, Folstein SW, McHugh PR (1975) Mini-mental state: a practical method of grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Gershon S, Yuwiler A (1960) Lithium ion: specific psychopharmacological approach to the treatment of mania. J Neuropsychiatr 1:229–241
Goldney RD, Spence ND (1986) Safety of the combination of lithium and neuroleptic drugs. Am J Psychiatry 143:882–884
Growe GA, Crayton JA, Klass DB, Evans H, Strizich M (1979) Lithium in chronic schizophrenia. Am J Psychiatry 136:454–455
Hirschowitz J, Casper R, Garver DL, Chang S (1980) Lithium response in good prognosis schizophrenia. Am J Psychiatry 137:916–920
Kane JM (1992) Clinical efficacy of clozapine in treatment-refractory schizophrenia: an overview. Br J Psychiatry 160 [suppl. 17]:41–45
Kane JM, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 45:789–796
Lewis HA, Bacher NM, Field PB (1986) Addition of lithium to neuroleptic treatment in chronic schizophrenia (letter). Am J Psychiatry 143:262
National Institute of Mental Health (1974) Abnormal involuntary movement scale. DHEW Publication (ADM) 9-117, Rockville, MD
National Institute of Mental Health (1987) Systematic assessment for treatment of emergent events. DHEW Publication (ADM) 9-112, Rockville, MD
Ortiz A, Gershon S (1986) The future of neuroleptic psychopharmacology. J Clin Psychiatry 47 [Suppl]:3–11
Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10:799–812
Pickar D, Owen RR, Litman RE (1991) New developments in the pharmacotherapy of schizophrenia. In: Tasman A, Goldfinger SM (eds) Review of psychiatry, Volume 10. American Psychiatric, Washington, DC, pp 98–115
Prakash R (1985) Lithium-responsive schizophrenia: case reports. J Clin Psychiatry 46:141–142
Prakash R, Kelwata S, Ban TA (1983) Neurotoxicity with combined administration of lithium and a neuroleptic. Comp Psychiatry 23:567–571
Simpson GM, Angus JWS (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 212:11–19
Small JG, Kellans JJ, Milstein V, Moore J (1975) A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J Psychiatry 132:1315–1317
Spitzer RL, Williams JBW, Gibbon M, First MB (1990) Structured clinical interview for DSM-III-R—patient edition (SCID-P, Version 1.0). American Psychiatric, Washington, DC
Wilson WH (1989) Diagnostic consultation to a state hospital. Hosp Commun Psychiatry 40:1290–1293
Wilson WH (1992) Clinical review of clozapine treatment in a state hospital. Hosp Commun Psychiatry 43:700–703
Zemlan FP, Hirschowitz J, Sauter F, Garver DL (1984) Impact of lithium therapy on core psychotic symptoms of schizophrenia. Br J Psychiatry 144:64–69
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Supported by Grant MH 46700 from the National Institute for Mental Health. Lithium and lithium placebo capsules were supplied by Lilly Pharmaceuticals
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Wilson, W.H. Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial. Psychopharmacology 111, 359–366 (1993). https://doi.org/10.1007/BF02244953
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DOI: https://doi.org/10.1007/BF02244953